Importance: Biomarkers for the early detection of Parkinsons disease (PD) are needed. Patients with PD display differences in peripheral blood biomarkers of immune function, including leukocyte differential counts and C-reactive protein (CRP), compared to controls. These differences may be useful biomarkers to predict PD, and may shed light on PD pathogenesis. Objectives: To identify whether peripheral immune dysregulation is a pre-diagnostic feature of PD, and whether it plays a causal role. Design: Cross-sectional association analysis of the relationship between differential leukocyte count and other markers of acute inflammation at enrolment, and incident cases of PD in UK Biobank. We used Mendelian randomization to establish whether differences in leukocyte differential counts have a causal influence on risk of PD. Setting: UK Biobank; a population-based cohort with over 500,000 participants aged 40-69 recruited in the UK between 2006 and 2010. Participants: PD cases were defined as individuals with an ICD-10 coded diagnosis of PD. Cases were defined as incident if their age at diagnosis was greater than their age at recruitment to UKB. Controls were defined as individuals without a diagnosis of PD. After applying exclusion criteria for pre-existing health conditions that can influence blood counts, 507 incident PD cases and 328,280 controls were included in the analysis. Exposure: Blood cell markers (absolute and relative counts) and other markers of inflammation were obtained from blood tests of participants taken at the initial visit. Results: Lower lymphocyte count was associated with increased odds of incident PD (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.65-0.90). There was weaker evidence of association between lower eosinophil and monocyte counts, lower CRP, and higher neutrophil counts on risk of incident PD. The association between lymphopenia and incident PD remained robust to sensitivity analyses. Mendelian randomization analyses suggested that the effect of low lymphocyte count on PD risk was causal (OR 0.91, 95% CI 0.85 - 0.99). Conclusions and relevance: In this large, prospective setting, lower lymphocyte count was associated with higher risk of subsequent PD diagnosis. Furthermore genetic evidence supported a causal role for lymphocyte count on PD risk.

中文翻译：

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淋巴细胞计数低是帕金森病的危险因素

重要性：需要早期发现帕金森病（PD）的生物标志物。与对照组相比，PD患者在免疫功能的外周血生物标志物方面存在差异，包括白细胞差异计数和C反应蛋白（CRP）。这些差异可能是预测PD的有用生物标记，并可能阐明PD的发病机理。目的：确定外周免疫功能异常是否是PD的预诊断特征，以及是否起因果作用。设计：横断面关联分析，分析了入选时白细胞计数与其他急性炎症标志物之间的关系，以及UK Biobank中的PD发病病例。我们使用孟德尔随机化来确定白细胞差异计数的差异是否对PD的风险有因果关系。地点：英国生物库；这是一项基于人群的队列研究，2006年至2010年期间在英国招募了500,000名年龄在40-69岁之间的参与者。参与者：PD病例定义为具有ICD-10编码的PD诊断的个体。如果病例的诊断年龄大于入职UKB的年龄，则定义为事件。对照被定义为没有诊断为PD的个体。在对可能影响血液计数的既有健康状况应用排除标准后，分析中包括了507例PD事件和328,280例对照。暴露：血细胞标志物（绝对和相对计数）和其他炎症标志物是从初次就诊时对参与者的血液测试中获得的。结果：较低的淋巴细胞计数与发生PD的几率增加相关（赔率[OR]为0.77，95％置信区间[CI]为0.65-0）。90）。较低的嗜酸性粒细胞和单核细胞计数，较低的CRP和较高的嗜中性粒细胞计数之间发生PD风险的关联性证据较弱。淋巴细胞减少症和入射PD之间的关联对敏感性分析仍然很可靠。孟德尔随机分析表明，低淋巴细胞计数对PD风险的影响是因果关系（OR 0.91，95％CI 0.85-0.99）。结论和相关性：在这种较大的前瞻性环境中，较低的淋巴细胞计数与随后的PD诊断的较高风险相关。此外，遗传证据支持了淋巴细胞计数对PD风险的因果作用。淋巴细胞减少症和入射PD之间的关联对敏感性分析仍然很稳健。孟德尔随机分析表明，低淋巴细胞计数对PD风险的影响是因果关系（OR 0.91，95％CI 0.85-0.99）。结论和相关性：在这种较大的前瞻性环境中，较低的淋巴细胞计数与随后的PD诊断的较高风险相关。此外，遗传证据支持了淋巴细胞计数对PD风险的因果作用。淋巴细胞减少症和入射PD之间的关联对敏感性分析仍然很稳健。孟德尔随机分析表明，低淋巴细胞计数对PD风险的影响是因果关系（OR 0.91，95％CI 0.85-0.99）。结论和相关性：在这种较大的前瞻性环境中，较低的淋巴细胞计数与随后的PD诊断的较高风险相关。此外，遗传证据支持了淋巴细胞计数对PD风险的因果作用。